Controversy guide update!

*Only for medical professionals to read and refer to the classification criteria, treatment, and guideline interpretation of gout
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The 8th Children's Rheumatism Immunity Summit Forum and the 14th National Children's Rheumatism and Immune Diseases Workshop will be held online from December 17th to 19th, 2021
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Rheumatologists and pediatricians from all over the country had heated discussions and academic sparks at the meeting
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Professor Zhang Xuewu from the Institute of Rheumatism and Immunity, Peking University People's Hospital, gave a presentation on the difficulties in the diagnosis and treatment of gout arthritis, from the trend of hyperuricemia in the younger generation, the classification standard of gout, to the treatment of gout, and the interpretation of gout guidelines in recent years.
Diagnosis and treatment of gout
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Hyperuricemia has a younger trend.
Gout is a metabolic arthritis caused by high uric acid, which must be paid attention to
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Hyperuricemia is defined as: fasting serum uric acid >420 μmol/L twice on different days (adults, regardless of male or female) under a normal purine diet
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When the blood uric acid level exceeds the joint monosodium urate saturation and precipitates and deposits in the peripheral joints and surrounding tissues, it is called gout
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In China, the prevalence of gout is 1.
6%, and the number of patients exceeds 22 million
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However, due to the blind spots and misunderstandings in the diagnosis and treatment of gout, and the differences of ethnic groups in the diagnosis and treatment of gout, the current situation of the diagnosis and treatment of gout in China is still worrying
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In recent years, studies have shown that the incidence of hyperuricemia presents a younger trend
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A survey of more than 20,000 freshmen in a university in Beijing from 2015 to 2017 showed that the prevalence of hyperuricemia was shocking, with the incidence of hyperuricemia in men reaching 37%, and the incidence of hyperuricemia in women was also 12.
8%.
%
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However, this result has been questioned.
Some experts believe that college freshmen have experienced a cruel college entrance examination, with little activity, excessive and irregular diet, which may promote hyperuricemia
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Therefore, a survey of more than 10,000 college graduates showed that there was no significant difference in the prevalence of hyperuricemia.
The incidence of hyperuricemia in men was 34%, and the incidence of hyperuricemia in women was also 10.
7%.

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Professor Zhang Xuewu pointed out that high uric acid is the basis of gout and hypertension, so for children, the identification and treatment of hyperuricemia is very important
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Figure 1 The prevalence of hyperuricemia in 23,497 new students from 2015 to 2017Figure 2 The prevalence of hyperuricemia in 12,839 graduates from 2015 to 2017 Clinical manifestations and classification criteria of gout Clinical manifestations of gout are divided into asymptomatic hyperuricemia Symptoms, acute gouty arthritis, intermittent periods, tophi formation and gout stages
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1// In the asymptomatic period, there is only fluctuating or persistent hyperuricemia.
The time from the increase of blood uric acid to the onset of symptoms can be several years, and some may remain symptom-free for life
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2// The acute arthritis stage and intermittent stage often have the following characteristics: (1) The onset of the disease usually occurs suddenly at midnight or in the early morning, with severe joint pain; the affected joint will appear red, swollen, hot, painful and dysfunctional within a few hours; (2) unilateral joint pain 1.
The metatarsophalangeal joint is the most common; 3.
The attack is self-limited and resolves spontaneously within 2 weeks; 4.
Colchicine can quickly relieve symptoms
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The intermittent period is the asymptomatic period between two gout attacks
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3// Tophi and Tophi in chronic arthritis are the characteristic clinical manifestations of gout
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Chronic arthritis is more common in patients without standard treatment.
The affected joints are asymmetrically swollen and painful, and a large number of tophi deposited in the joints can cause joint bone destruction
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The classification criteria currently adopts the gout classification criteria jointly developed by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) in 2015
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Step 1: Applicable criteria (this standard can only be applied if the admission criteria are met): There is swelling, pain or tenderness of at least one peripheral joint or bursa; Step 2: Determine the criteria (gold standard, direct diagnosis, no need to enter into the classification diagnosis) : Polarized light microscope examination confirmed the presence of sodium urate crystals in (formerly) symptomatic joints or bursae or tophi; Step 3: Classification criteria (when the admission criteria are met but the determination criteria are not met): ≥ 8 points for diagnosis for gout
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Figure 3 Gout classification criteria jointly formulated by ACR and EULAR in 2015 Treatment of refractory gout Professor Zhang Xuewu pointed out that gouty arthritis itself is easier to control, and treatment with uric acid-lowering drugs and anti-inflammatory treatment during acute attacks can be controlled at an ideal level level
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However, due to its early and intermittent attacks, patients do not pay attention to it, resulting in gout complications, and many difficulties are encountered in the treatment of uric acid lowering during the attack of gouty arthritis
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Refractory gout refers to at least one of the following three conditions: sufficient dose and full course of conventional uric acid-lowering drugs are used alone or in combination, but blood uric acid is still ≥360 μmol/L; gout attacks are still ≥2 times/year after standardized treatment; Multiple and/or progressive tophi
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The focus of refractory gout is the treatment of acute gouty arthritis with comorbidities: diabetic nephropathy, gouty arthritis attack in renal insufficiency; acute gout attack in patients with peptic ulcer; how to lower uric acid in patients with fatty liver and kidney stones? How to lower uric acid in patients with myocardial infarction complicated with renal insufficiency? Professor Zhang Xuewu pointed out that the treatment principle of acute gouty arthritis with complications is to use non-steroidal anti-inflammatory drugs for acute gouty arthritis (with diabetes); use glucocorticoids for renal insufficiency; use hormones with caution when combined with hypertension; NSAIDs should be used with caution in patients with coronary heart disease; biological agents should be used in patients with ulcer disease, diabetes and renal insufficiency
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Interpretation of the "2020 ACR Gout Management Guidelines" This guideline emphasizes on-target treatment; emphasizes that uric acid-lowering drug treatment should be given as soon as possible while fully anti-inflammatory during acute exacerbation; emphasizes that preventive anti-inflammatory treatment should be given along with uric acid-lowering treatment; no longer emphasizes Alkalize urine; emphasize long-term medication control
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Professor Zhang Xuewu pointed out that the suggestion to "administer uric acid-lowering drug therapy as soon as possible while fully anti-inflammatory during acute exacerbation" has caused controversy among rheumatologists, who believe that uric acid-lowering therapy during acute exacerbation may delay the time of inflammation
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In addition, alkalized urine can promote uric acid excretion and inhibit stone formation, so the de-emphasis of alkalized urine is also controversial
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1.
Indications for initial urate-lowering therapy (ULT) It is strongly recommended to initiate urate-lowering therapy in gout patients with any of the following characteristics: 1 or more subcutaneous tophi
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There is evidence of any form of imaging impairment due to gout
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Frequent gout (>2 times/year)
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For patients who have experienced more than one acute gout attack, but infrequent (<2 times/year), initiation of ULT treatment is conditionally recommended; for gout patients with a first gout attack, it is conditionally recommended not to initiate ULT treatment
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However, the initiation of ULT is conditionally recommended for the following patients: patients with moderate to severe chronic kidney disease (CKD>3), serum uric acid (SU) >9 mg/dL (535.
5 μmol/L), or urolithiasis
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In patients with asymptomatic hyperuricemia, there is a conditional recommendation not to initiate ULT
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2.
Recommendations for initial ULT in gout patients Allopurinol is strongly recommended as the first-line drug of choice for ULT, including in patients with moderate and severe CKD (CKD>3 stage); strongly recommended in patients with moderate and severe CKD (CKD>3 stage) , allopurinol and febuxostat were selected in priority over probenecid
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Pegloticase is strongly not recommended as a first-line option
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It is recommended to start with a low dose and then gradually titrate: the initial dose of allopurinol is <100mg/d (for patients with CKD>3, the dose should be lower); the initial dose of febuxostat is <40mg/d; probenecid starts The starting dose is 500 mg, qd or bid (conditional recommendation for low-dose probenecid starting)
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At the same time, anti-inflammatory preventive treatment is carried out, and drugs such as colchicine, non-steroidal anti-inflammatory drugs, and prednisone/prednisolone are selected
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Continue concurrent anti-inflammatory prophylaxis for 3-6 months, rather than <3 months, and continue to evaluate patients and anti-inflammatory prophylaxis if they continue to experience gout flares
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3.
Timing of ULT initiation For all patients receiving ULT treatment, it is strongly recommended to adopt an on-target treatment strategy, that is, titrating the dose of ULT based on continuously measured SU levels to achieve the SU target, rather than a fixed-dose ULT strategy
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For all patients treated with ULT, a SU target of <6 mg/dL (360 μmol/L) is strongly recommended and maintained
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For all patients treated with ULT, augmentation of ULT dose management by a non-physician provider is conditionally recommended to optimize treatment target strategies, including, for example, patient education, shared decision-making, and targeted therapy
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4.
Recommendations for the use of ULT specific drugs 5.
Controversy in the management guidelines for acute gout.
The latest opinion Professor Zhang Xuewu pointed out that the "2020 ACR Gout Management Guidelines" pointed out the direction for gout treatment, but there were also some problems
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The 2021 issue of The Lancet, based on controversial questions, pointed out the need to alkalize urine, drink plenty of water and alkalize urine while taking uric acid-boosting drugs such as benzbromarone, Avoid urinary stone formation
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The optimal pH of morning urine is 6.
2-6.
9, and the urine is alkalized when the pH of morning urine is less than 6.
0, especially when taking uricosuric drugs
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Sodium bicarbonate is suitable for patients with chronic renal insufficiency combined with metabolic poisoning, while citrate preparations are suitable for patients with uric acid nephrolithiasis
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In addition, in response to the "2020 ACR Gout Management Guidelines" that emphasizes "sufficient anti-inflammatory and uric acid-lowering drug treatment as soon as possible during acute attacks", the "Lancet" pointed out that SU fluctuations can lead to acute gout attacks, and most gout guidelines are It is not recommended to use uric acid-lowering drugs at the beginning of an acute gout attack, and should be used as appropriate after 2 weeks of anti-inflammatory and analgesic treatment
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The target of uric acid lowering treatment for gout patients is SU<360 μmol/L, and long-term maintenance; if the patient has tophi, chronic gouty arthritis or frequent gouty arthritis attacks, the target of uric acid lowering treatment is SU<300 μmol/L, until If the tophi is completely dissolved and the symptoms of frequent arthritis are improved, the treatment target can be changed to SU<420 μmol/L and maintained for a long time
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But SU is not as low as possible, usually should not be lower than 180 μmol/L
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In conclusion, gout is a metabolic disease that seriously affects the quality of life of patients.
The treatment of gout is still controversial and in the process of continuous development
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Professor Zhang Xuewu introduced the diagnosis and treatment of gout in an all-round way from the trend of hyperuricemia in the younger generation, the classification standard of gout, the treatment of gout, and the interpretation of gout guidelines in recent years, and pointed out the direction for the diagnosis and treatment of gout
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Expert Profile Professor Zhang Xuewu is a professor at the Clinical Immunity Center/Rheumatic Immunity Institute of Peking University People's Hospital, chief physician, doctor of medicine, and doctoral tutor
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National Standing Committee Member of Rheumatology Branch of Chinese Medical Association, Standing Committee Member of Beijing Rheumatology Branch of Chinese Medical Association
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Member of the National Standing Committee of the Rheumatology Branch of the Chinese Medical Doctor Association, Secretary General of the Osteoporosis Group, and Vice Chairman of the Beijing Rheumatology Branch of the Chinese Medical Doctor Association
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Member of the National Standing Committee of the Bone and Joint and Rheumatology Branch of the Chinese Association of Rehabilitation Medicine
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